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Profibrotic effects of endothelin-1 via the ETA receptor in cultured human cardiac fibroblasts

Hafizi, Sassan LU ; Wharton, J; Chester, AH and Yacoub, MH (2004) In Cellular Physiology and Biochemistry 14(4-6). p.285-292
Abstract
Background/Aims: Endothelin-1 (ET-1) has been implicated in pathologic remodelling and tissue repair processes in the heart. We investigated the effects of ET-1 on growth and collagen synthesis responses in cardiac fibroblasts isolated from human hearts. We also studied the receptor subtype(s) mediating such responses and the factors regulating their expression. Methods: Fibroblasts were isolated from cardiac transplant recipient hearts and characterised by immunocytochemistry. Serum-starved cells were exposed to ET-1 and incorporation of [H-3]proline and thymidine were measured as indexes of collagen and DNA synthesis respectively. Blocking experiments utilised the selective ETA receptor antagonist BQ123 and the ETB antagonist BQ788.... (More)
Background/Aims: Endothelin-1 (ET-1) has been implicated in pathologic remodelling and tissue repair processes in the heart. We investigated the effects of ET-1 on growth and collagen synthesis responses in cardiac fibroblasts isolated from human hearts. We also studied the receptor subtype(s) mediating such responses and the factors regulating their expression. Methods: Fibroblasts were isolated from cardiac transplant recipient hearts and characterised by immunocytochemistry. Serum-starved cells were exposed to ET-1 and incorporation of [H-3]proline and thymidine were measured as indexes of collagen and DNA synthesis respectively. Blocking experiments utilised the selective ETA receptor antagonist BQ123 and the ETB antagonist BQ788. Results: ET-1 elicited a potent collagen synthesis response in cardiac fibroblasts, with a maximum 29+/-5% increase that was abolished by BQ123. Cardiac fibroblasts responded to ET-1 with a concentration-dependent decrease to those of TGF-beta. Radioligand binding studies revealed the presence of high-affinity ET-1 binding sites on these cells, which were upregulated by treatment with the growth factors PDGF and EGF but downregulated by TGF-beta. Conclusions: These results therefore implicate ET-1 as a trophic agent in the human heart with the ability to influence the development of cardiac fibrosis. Copyright (C) 2004 S. Karger AG, Basel. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
factors, collagen, fibroblast, cardiac, human, endothelin, receptors, growth
in
Cellular Physiology and Biochemistry
volume
14
issue
4-6
pages
285 - 292
publisher
Karger
external identifiers
  • wos:000223489700012
  • pmid:15319532
  • scopus:4444381213
ISSN
1015-8987
DOI
10.1159/000080338
language
English
LU publication?
yes
id
ae2ea49f-9b35-4e1e-83ae-318955a21ec8 (old id 269315)
date added to LUP
2007-10-29 09:58:21
date last changed
2017-10-22 04:45:23
@article{ae2ea49f-9b35-4e1e-83ae-318955a21ec8,
  abstract     = {Background/Aims: Endothelin-1 (ET-1) has been implicated in pathologic remodelling and tissue repair processes in the heart. We investigated the effects of ET-1 on growth and collagen synthesis responses in cardiac fibroblasts isolated from human hearts. We also studied the receptor subtype(s) mediating such responses and the factors regulating their expression. Methods: Fibroblasts were isolated from cardiac transplant recipient hearts and characterised by immunocytochemistry. Serum-starved cells were exposed to ET-1 and incorporation of [H-3]proline and thymidine were measured as indexes of collagen and DNA synthesis respectively. Blocking experiments utilised the selective ETA receptor antagonist BQ123 and the ETB antagonist BQ788. Results: ET-1 elicited a potent collagen synthesis response in cardiac fibroblasts, with a maximum 29+/-5% increase that was abolished by BQ123. Cardiac fibroblasts responded to ET-1 with a concentration-dependent decrease to those of TGF-beta. Radioligand binding studies revealed the presence of high-affinity ET-1 binding sites on these cells, which were upregulated by treatment with the growth factors PDGF and EGF but downregulated by TGF-beta. Conclusions: These results therefore implicate ET-1 as a trophic agent in the human heart with the ability to influence the development of cardiac fibrosis. Copyright (C) 2004 S. Karger AG, Basel.},
  author       = {Hafizi, Sassan and Wharton, J and Chester, AH and Yacoub, MH},
  issn         = {1015-8987},
  keyword      = {factors,collagen,fibroblast,cardiac,human,endothelin,receptors,growth},
  language     = {eng},
  number       = {4-6},
  pages        = {285--292},
  publisher    = {Karger},
  series       = {Cellular Physiology and Biochemistry},
  title        = {Profibrotic effects of endothelin-1 via the ETA receptor in cultured human cardiac fibroblasts},
  url          = {http://dx.doi.org/10.1159/000080338},
  volume       = {14},
  year         = {2004},
}